The NNTRC's Applied Research Program will provide resources to support the improvement of the products and services that the NNTRC provides to its user community. These efforts will be focused on areas of research where the improvement in products and services can have the most significant impact on venom- related research. In the next grant period, the Applied Research Program will focus on two very specific areas: 1) the application of new methods and approaches to the production of medically significant recombinant snake venom toxins and 2) the development of novel cell-based assays that can be used for the testing of anti- venoms and toxin inhibitory molecules. One of the major areas of emphasis in the coming grant period will be improvements in the production of recombinant snake venom toxins to address the growing demand for recombinant toxins to support both pharmaceutical and anti-venom research. The NNTRC will conduct a program of applied research with the goal of expanding and improving the NNTRC's capacity to produce medically important recombinant venom proteins. While some venom toxins are relatively easy to produce using conventional molecular technologies, many others are difficult to produce in an active form due to insolubility, extensive intramolecular cross-linking and post-translational modifications. Recent advances in the field of recombinant protein production has opened the door to the application of new approaches to improving the production of ?recalcitrant? recombinant proteins. In the next grant period, the NNTRC will explore the use of these new methods to improve the Center's ability to produce a broad spectrum of recombinant snake venom toxins. In addition, during the next funding period, the NNTRC will conduct applied research on the development and validation of new in vitro screening assays that can be used to profile the activity of novel snake venom toxin antidotes. These cell-based assays will not only reduce the use of animals for toxicity testing but will also provide specialized research services to support the discovery and optimization of the next generation of snake venom antidotes.!